NDT Advance Access originally published online on January 18, 2006
Nephrology Dialysis Transplantation 2006 21(5):1270-1277; doi:10.1093/ndt/gfk043
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
PAF-acetylhydrolase activity in plasma of patients with chronic kidney disease. Effect of long-term therapy with erythropoietin
1 Laboratory of Biochemistry, Department of Chemistry and 2 Division of Nephrology, Department of Internal Medicine, University of Ioannina, 45110 Ioannina, Greece
Correspondence and offprint requests to: Dr Alexandros D. Tselepis, MD, PhD, Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Email: atselep{at}cc.uoi.gr
Background. Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+-independent phospholipase A2 that is secreted mainly from monocytes/macrophages. In human plasma, PAF-AH is associated primarily with low-density lipoprotein (LDL), while a small proportion of enzyme is associated with high-density lipoprotein (HDL). The ratio of HDL–PAF-AH to total plasma enzyme activity may represent a potential marker of atherogenicity. We evaluated possible alterations of lipoprotein-associated enzyme activity in Chronic Kidney Disease (CKD) patients, stages 3–4, and further investigated whether long-term therapy with recombinant human erythropoietin (epoetin) has any influence on the plasma PAF-AH activity in vivo or on the enzyme activity secreted from peripheral blood monocytes (PBMs), in vitro.
Methods. Forty-eight patients, 28 men and 20 women, with CKD (stages 3–4) participated in the study. Patients were randomized into groups I and II. Patients of group I (n = 28) were administered subcutaneously epoetin, 50 units/kg once per week. The Hb target was 13 g/dl. In group II (n = 20), epoetin was initiated only when the Hb levels decreased during follow-up to less than 9 g/dl. All patients were seen on an outpatient basis at 2, 4 and 6 months. Twenty-two normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls.
Results. The PAF-AH activity in plasma of both patient groups at baseline was higher compared to controls, whereas no difference in the HDL–PAF-AH activity was observed among the studied groups. Thus, the ratio of HDL–PAF-AH to the plasma enzyme activity was significantly lower in both patient groups compared to controls. Epoetin administration in the patients of group I was associated with a significant increase in the plasma PAF-AH and in HDL–PAF-AH activities 2 months after treatment, which remained stable for up to 6 months of therapy, a phenomenon not observed in untreated patients of group II. Thus, the ratio of HDL–PAF-AH to the plasma enzyme activity was significantly increased in patients of group I compared to the baseline values, a phenomenon not observed in patients of group II. In vitro treatment with epoetin of PBMs from patients of group I (undergoing therapy with epoetin) resulted in a dose-dependent increase in total and secreted enzyme activity, a phenomenon not observed in patients of group II who did not receive therapy with epoetin. This suggests that the in vivo increase in lipoprotein-associated PAF-AH observed in patients treated with epoetin may be attributed to the drug-induced enhanced secretion of PAF-AH from PBMs of these patients.
Conclusions. CKD patients of stages 3–4 are characterized by an increase in plasma PAF-AH activity and a low ratio of HDL–PAF-AH to total plasma enzyme activity. Long-term therapy with epoetin may improve this atherogenic ratio thus this drug may play an important antiatherogenic role in CKD.
Keywords: chronic kidney disease; epoetin; lipoproteins; monocytes; PAF-acetylhydrolase; paraoxonase-1
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